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1.
Blood ; 134(2): 211-215, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31151984

RESUMO

At Massachusetts General Hospital, we pioneered simultaneous hematopoietic cell (HCT)/kidney transplantation from HLA-identical related donors for the treatment of hematological malignancies with end-stage renal failure. We have now extended this to HLA-haploidentical donors in a pilot trial. Six recipients, 5 of whom were conditioned with fludarabine, cyclophosphamide, and total-body irradiation, underwent combined HCT/kidney transplantation from haploidentical donors; graft-versus-host disease (GVHD) prophylaxis included post-HCT cyclophosphamide, tacrolimus, and mycophenolate mofetil. One patient died as a result of complications of fludarabine neurological toxicity. No neurological toxicity was observed in subsequent patients who received lower fludarabine doses and more intense postfludarabine dialysis. There were no cases of grade 2 to 4 acute GVHD and 1 case of moderate chronic GVHD by 12 months. One patient experienced relapse of multiple myeloma at 30 months after HCT and died 4 years posttransplantation. Overall, 4 of 6 patients remain alive, without disease relapse and with long-term renal rejection-free survival. This trial was registered at www.clinicaltrials.gov as #NCT01758042.


Assuntos
Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Transplante Haploidêntico/métodos , Adulto , Idoso , Feminino , Neoplasias Hematológicas/complicações , Humanos , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/epidemiologia , Condicionamento Pré-Transplante/métodos
2.
Int J Hematol ; 110(1): 30-38, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104211

RESUMO

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide has spread rapidly worldwide. This strategy was initially developed in the setting of bone marrow transplantation following nonmyeloablative conditioning. Recently, peripheral blood stem cell grafts and/or myeloablative conditioning regimen have been widely used. In Japan, prospective, multicenter, phase II studies have been conducted by the Japan Study Group for Cell Therapy and Transplantation to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haploPBSCT). In the first such study (JSCT Haplo 13 study), we demonstrated that PTCy-haploPBSCT after busulfan-based reduced-intensity conditioning (RIC) enables stable donor engraftment and low incidences of both acute and chronic graft-versus-host disease (GVHD). In the second (JSCT Haplo 14 study), we showed that both myeloablative conditioning (MAC) and RIC are valid options for PTCy-haploPBSCT. Emerging evidence, including our findings, suggests that donor type (HLA-haploidentical donor versus HLA-matched related or unrelated donor) may no longer be a significant predictor of transplant outcome.


Assuntos
Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Haploidêntico/métodos , Ensaios Clínicos como Assunto , Humanos , Japão
3.
BMC Cancer ; 19(1): 242, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885156

RESUMO

BACKGROUND: Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG). CASE PRESENTATION: Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient's general condition remains good. CONCLUSIONS: This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Decitabina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Cladribina/uso terapêutico , Citarabina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Indução de Remissão/métodos , Terapia de Salvação/métodos , Irmãos , Transplante Haploidêntico/métodos , Resultado do Tratamento
4.
J Immunol ; 202(7): 2141-2152, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30787107

RESUMO

Little is known regarding the effect of KIR/HLA incompatibilities (inc.) in the setting of T-replete haploidentical allogeneic hematopoietic stem cell transplantation using posttransplant cyclophosphamide (PTCy). In this retrospective study, the impact of KIR/HLA inc. on clinical outcomes and NK cell reconstitution was studied in a cohort of 51 consecutive patients receiving a T cell-replete haploidentical allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning using peripheral blood stem cells as the source of the graft and PTCy as graft-versus-host disease (GvHD) prophylaxis. The NK cell repertoire reconstitution was examined by multiparameter flow cytometry in 34 of these 51 patients from day 0 to day 100 posttransplant. Genetic KIR2DL/HLA inc. were found to be significantly associated with more GvHD (81.2 versus 45.7%, p = 0.01) and less relapse (6.2 versus 42.8%, p = 0.008) in this context. GvHD is associated with increased levels of differentiated and activated NK cells. A significant loss of KIR2DL2/3+ NK cells was observed at day 30 in patients with inhibitory KIR/HLA inc., suggesting that responsive KIR NK cells are particularly targeted by the immunosuppressive PTCy treatment. Further investigations are needed from a larger cohort with an identical clinical approach to consolidate these results and to identify the NK cell subsets that may be beneficial for the graft-versus-leukemia effect observed. Because many haploidentical donors can be identified in a family, the prediction of KIR NK cell alloreactivity could be of crucial importance for donor selection and patient outcome.


Assuntos
Efeito Enxerto vs Leucemia/imunologia , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Células Matadoras Naturais/imunologia , Receptores KIR/genética , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos/imunologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transplante Haploidêntico/métodos , Resultado do Tratamento
5.
Crit Rev Oncol Hematol ; 133: 120-128, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30661648

RESUMO

BACKGROUND: Peripheral-blood (PB) and bone marrow (BM) are both widely used in hematopoietic stem cell transplantation (HSCT). However, it is unclear whether PB or BM produces a more satisfactory outcome in haploidentical HSCT, particularly for patients using post-transplant cyclophosphamide (PTCy), which is the standard therapy. However, to date, no meta-analysis focusing on this issue has been published. METHODS: We systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding the use of BM or PB in haploidentical HSCT for hematological malignancies in adults using PTCy. Data were analyzed using Open Meta-Analyst statistical software. RESULTS: Fourteen studies were extracted including four comparative retrospective reports and ten single-arm reports, with a total of 1759 patients received PTCy haploidentical HSCT (462 patients received PBSCT, 1297 patients received BMT). The pooled outcomes of comparative retrospective studies showed significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (OR = 1.741, 95%CI 1.032-2.938), incidence of grade IIIV acute GVHD (OR = 1.778, 95%CI 1.314, 2.406) and engraftment rate (OR = 1.843, 95%CI 1.066-3.185) in the PB group. No significant differences were found on the incidence of relapse, 2-year overall survival (OS) and disease-free survival (DFS), acute IIIV GVHD and chronic GVHD between PBSCT or BMT. CONCLUSION: The efficacy of PB is not inferior to BM for patients undergoing PTCy haploidentical HSCT with regard to primary outcomes, including OS, DFS, NRM and relapse. However, with regards to convenience and pain relief, PB graft is suitable for haploidentical HSCT, but with a higher risk of acute GVHD.


Assuntos
Transplante de Medula Óssea/métodos , Ciclofosfamida/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico , Adulto , Transplante de Medula Óssea/efeitos adversos , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doadores de Tecidos , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/métodos
6.
Eur J Haematol ; 102(3): 256-264, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30578673

RESUMO

OBJECTIVES: To establish the optimal strategy for haploidentical hematopoietic stem cell transplantation (HSCT). METHODS: We performed a prospective study on haploidentical HSCT using low-dose alemtuzumab. Alemtuzumab was added at 0.25 mg/kg for 2 days. The primary outcome measure was the survival rate with the engraftment of donor cells and without grade III-IV acute graft-vs-host disease (GVHD) at 60 days after transplantation. RESULTS: Fourteen adult patients with advanced hematological disease were enrolled. The primary outcome measure was achieved in 86% of the patients. Six patients experienced relapse/progression. Non-relapse death was observed in three patients, and all of them had a history of previous allogeneic HSCT. Overall survival and progression-free survival rates at 1 year were 51% and 43%, respectively. Four patients were suspected to have herpes simplex virus infection and three had aseptic meningitis under the use of acyclovir at 200 mg. There were no deaths due to viral infection. Compared to those who underwent haploidentical HSCT using thymoglobulin, patients with alemtuzumab showed a slower recovery of CD8+ T-cells and lower incidences of GVHD and EB virus reactivation. CONCLUSIONS: Haploidentical HSCT using low-dose alemtuzumab can be performed safely. We need to overcome the high relapse/progression rate in non-remission patients.


Assuntos
Alemtuzumab/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Transplante Haploidêntico , Adolescente , Adulto , Idoso , Soro Antilinfocitário/administração & dosagem , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Haplótipos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
7.
Biol Blood Marrow Transplant ; 25(3): 529-537, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30481596

RESUMO

This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n = 83, group A) or high risk; patients at high risk were randomly assigned to receive (n = 72, group B) or not receive (n = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100days after transplantation (hazard ratio, 1.547; P = .015) and platelet recovery (hazard ratio, 1.456; P = .037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.).


Assuntos
Intervalo Livre de Doença , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Metilprednisolona/uso terapêutico , Pré-Medicação/métodos , Transplante Haploidêntico , Adulto , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/etiologia , Seguimentos , Glucocorticoides/farmacologia , Humanos , /etiologia , Masculino , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Transplante Haploidêntico/métodos , Transplante Haploidêntico/mortalidade , Transplante Homólogo
8.
Sci China Life Sci ; 62(1): 104-111, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29869037

RESUMO

To compare the efficacy of HLA6/6-matched haploidentical hematopoietic stem cell transplant (haplo-HSCT) with that of HLA3/6-matched HSCT in T-cell-replete transplants, we recruited 27 consecutive recipients from multiple centers who received HLA6/6-matched haplo-HSCT from a parent or child donor between February 2010 and May 2016. A matched-pair analysis was designed. For each recipient from the study cohort, two recipients were randomly selected from the control cohort and matched (according to patient age, patient sex, disease type, disease status, donor age, donor sex, and recipient-donor relationship). No significant differences were found in hematopoietic recovery. The incidence of grade II-IV and III-IV acute graft versus host disease was similar (18.5% vs. 31.5%, P=0.216; 11.1% vs. 9.3%, P=0.792) in the HLA6/6 and HLA3/6 groups, respectively. The 3-year cumulative incidence of relapse was 14.8% and 17.0% (P=0.800). The 3-year cumulative incidence of nonrelapse mortality was 12.1% and 17.6% (P=0.751). The estimated 3-year disease-free survival was 73.1% and 65.5% (P=0.489). The estimated 3-year overall survival was 74.7% and 74.0% (P=0.946). The data suggested the efficacy and safety of the HLA6/6- and the HLA3/6-matched haplo-HSCT between parents and children are comparable. That HLA-mismatch disparity is not correlated with T-cell-replete haplo-HSCT outcome was substantiated.


Assuntos
Antígenos HLA/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade/métodos , Linfócitos T/imunologia , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pais , Adulto Jovem
9.
J Pediatr Hematol Oncol ; 41(3): e158-e160, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30044345

RESUMO

Allogeneic hematopoietic stem cell transplant (HSCT) has been known to be a curative therapy for patients with hemophagocytic lymphohistiocytosis (HLH) but donor availability is an issue. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) has been investigated as a feasible option for various malignant and nonmalignant conditions with reduced incidence of acute graft versus host disease (GVHD) and graft rejection. However, its use has not been described in children with HLH and here we describe 2 boys who underwent successful haploidentical HSCT with PTCy. None had acute GVHD and 1 had limited chronic GVHD. Both are alive and disease-free at follow-up of 912 and 239 days, respectively. Haploidentical HSCT with PTCy is a feasible option for children with HLH lacking a matched sibling donor.


Assuntos
Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfo-Histiocitose Hemofagocítica/terapia , Transplante Haploidêntico/métodos , Criança , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Doadores de Tecidos/provisão & distribução , Transplante Haploidêntico/efeitos adversos , Resultado do Tratamento
10.
J Glob Oncol ; 4: 1-13, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30521413

RESUMO

Use of haploidentical (haplo) donors for hematopoietic cell transplantation (HCT) has significantly increased in the last decade. The major advantage with this strategy is universal availability and faster acquisition of the donor, along with affordability and provision of immunotherapy in post-transplantation period. Historically, haplo-HCT was associated with compromised outcomes because of high rates of graft-versus-host disease and graft failure, but after the development of a post-transplantation high-dose cyclophosphamide strategy, which results in selective T-cell depletion, these issues have been addressed to a large extent. Nevertheless, graft failure, high treatment-related mortality due to graft-versus-host disease, infections, delayed immune reconstitution, and disease relapse remain significant concerns. As the experience with haplo-HCTs grows, the clinical outcomes are becoming more at par with those seen with fully matched unrelated donor allogeneic HCTs.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Humanos
13.
Curr Opin Oncol ; 30(6): 396-401, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30307414

RESUMO

PURPOSE OF REVIEW: Nowadays, T-cell-depleted haploidentical transplantation is considered a valid approach for children lacking a human leukocyte antigen (HLA) identical donor for allogeneic transplantation. This kind of allogeneic transplant is now widely used especially for pediatric patients with high-risk hematological malignancies. However, relapsing disease and life-threatening viral infections are still relevant clinical problems as a consequence of delayed immune reconstitution. Adoptive cell therapies have been proposed to overcome this problem. RECENT FINDINGS: After initial clinical approach using CD34+ selection as method for T-cell depletion (TCD), it was observed that immune reconstitution was delayed and it resulted on high incidence of opportunistic infections and nonrelapse mortality. It is now evident that development over time of graft manipulation techniques for TCD, have provide clinicians a useful tool for overcoming transplant complication such as graft failure, severe graft-vs.-host disease and opportunistic infections. As such, several procedures of almost total or partial TCD have been developed including CD3/CD19 depletion, T cell receptor αß/CD19 depletion and more recently CD45RA+ depletion. Recent studies showed that immune reconstitution is associated with transplant outcomes. Based on this, haploidentical transplantation is now been explored as platform for cellular therapy to prevent disease recurrence or to treat clinical complications. SUMMARY: Allogeneic transplantation still remains a standard of care for pediatric patients with high-risk hematological malignancies. In absence of an HLA identical donor, T-cell-depleted haploidentical transplant is now considered a valid option and provide a platform for cellular therapy to prevent relapse disease or to treat opportunistic infections.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Depleção Linfocítica/métodos , Linfócitos T/imunologia , Transplante Haploidêntico/métodos , Criança , Neoplasias Hematológicas/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunologia de Transplantes , Transplante Homólogo
14.
Am J Hematol ; 93(12): 1524-1531, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30194866

RESUMO

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30; MDS n = 3; median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis. No graft rejection was observed. Complete remission at day +30 was achieved in 97% of patients. CI of acute GvHD grade II-IV and chronic GvHD was 24% (no grade IV) and 23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen-related toxicities (grade III-IV) were observed in 58%, predominantly involving the gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a median follow-up of 36 months, the estimated 1- and 3-year overall survival was 56% and 48%. Disease-free survival was 49% and 40%, respectively. At 3 years, GvHD and relapse-free survival (GRFS) was 24% while chronic GvHD and relapse-free survival (CRFS) was 29%. Thus, our results indicate that sequential haplo-HSCT is an effective salvage treatment providing high anti-leukemic activity, favorable tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Transplante Haploidêntico/métodos , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Terapia de Salvação/métodos , Resultado do Tratamento
15.
J Hematol Oncol ; 11(1): 110, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-30165887

RESUMO

BACKGROUND: Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established. METHODS: This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics. RESULTS: SUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002). CONCLUSIONS: Our results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.


Assuntos
Bussulfano/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Leucemia Mieloide Aguda/terapia , Tiotepa/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Vidarabina/análogos & derivados , Adulto , Idoso , Bussulfano/farmacologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Tiotepa/farmacologia , Condicionamento Pré-Transplante/mortalidade , Transplante Haploidêntico/mortalidade , Vidarabina/farmacologia , Vidarabina/uso terapêutico , Adulto Jovem
16.
Pediatr Transplant ; 22(7): e13279, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30091256

RESUMO

Use of TCR α+ ß+ /CD19+ depletion in a pediatric setting has improved the utility of haploidentical donor material, resulting in better rates of engraftment, lower rates of graft vs host disease (GVHD), and improved transplant-related mortality. There are currently no data available on the costs of TCR α+ ß+ /CD19+ depletion. This study assessed the costs of acquiring and preparing TCR α+ ß+ /CD19+ depleted haploidentical donor cells in comparison with matched unrelated donor (MUD) products for use in pediatric patients in Australia. Data from four pediatric transplant centers were used to estimate the resources required for donor work-up, graft acquisition, and laboratory procedures for graft preparation. Information on MUD work-up and graft acquisition was also acquired from these sites and from the national coordinating donor center in Australia. Australian-specific prices and fees were used to estimate total average costs for each transplant type, converted to USD. Preparation of graft material (including work-up, acquisition, and laboratory processes) costs USD 28 963 for TCR α+ ß+ /CD19+ depleted haploidentical grafts and USD 27 297 for MUD grafts. The estimated difference of USD 1666 is largely attributed to the process and consumables to perform TCR α+ ß+ /CD19+ depletion. Given the potential for recipients of TCR α+ ß+ /CD19+ depleted grafts to require minimal GVHD prophylaxis and experience less transplant-related morbidity and mortality, use of TCR α+ ß+ /CD19+ depletion appears favorable despite the higher initial cost. Research is currently ongoing to assess the clinical effectiveness and potential cost-effectiveness of TCR α+ ß+ /CD19+ depletion over a patients' lifetime.


Assuntos
Antígenos CD19/metabolismo , Custos de Cuidados de Saúde/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/economia , Depleção Linfocítica/economia , Linfócitos T/metabolismo , Transplante Haploidêntico/economia , Doadores não Relacionados , Austrália , Biomarcadores/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Depleção Linfocítica/métodos , Transplante Haploidêntico/métodos
17.
Intern Med J ; 48(8): 988-991, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30133987

RESUMO

Graft failure affects approximately 5% of allogeneic stem cell transplants, with a poor prognosis. Salvage second allogeneic stem cell transplantation (alloSCT2) is limited by high rates of transplant-related mortality from infection and graft-versus-host disease. We report on five adult patients receiving rescue alloSCT2 using haploidentical peripheral blood stem cells. All patients achieved neutrophil engraftment, two subsequently died from sepsis and disease relapse, respectively. Three patients remain alive up to 2 years post-transplant. We suggest consideration of haploidentical alloSCT2 for patients with graft failure.


Assuntos
Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/fisiologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Terapia de Salvação/métodos , Transplante Haploidêntico/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/tendências , Terapia de Salvação/tendências , Transplante Haploidêntico/tendências , Falha de Tratamento , Adulto Jovem
18.
Am J Hematol ; 93(11): 1368-1375, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30117176

RESUMO

This prospective study explored an optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with severe aplastic anemia (SAA) who received haplo-identical stem cell transplantation from a related mismatched donor (Haplo-SCT). We explored a safe and sufficient dose of rabbit ATG (Thymoglobulin) in combination with 800 cGy total body irradiation (TBI) and fludarabine (Flu, 30 mg/m2 /day) for 5 days using step-by-step dose de-escalation. The dose of ATG was de-escalated from 10 mg/kg (group 1), to 7.5 mg/kg (group 2), to 5 mg/kg (group 3), and the TBI dose was reduced to 600 cGy (group 4) beginning in October 2014. If one patient developed transplant-related mortality (TRM) with engraftment in a group, we moved to the next lower dose group. Thirty-four patients were enrolled in groups 1-3 (n = 10) and 4 (n = 24). All patients achieved primary engraftment. The incidence of acute GVHD (grade ≥ 2) and chronic GVHD (≥ moderate) was 29.4% and 14.7%, respectively. With a median follow-up of 56.6 and 21.8 months in groups 1-3 and group 4, respectively, the 2-year probability of overall survival (91.7% in group 4 vs 70% in groups 1-3, P = 0.155) and GVHD-free survival (78.4% in group 4 vs 50% in groups 1-3, P = 0.115) was shown tended to be better in group 4. This study explored an optimal conditioning with step-by-step de-escalation dosage of ATG and TBI to reduce TRM with sustained graft function. TBI-600 cGy/Flu/intermediate-dose ATG resulted in feasible outcomes of Haplo-SCT for adult patients with SAA.


Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/administração & dosagem , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Irradiação Corporal Total/métodos , Adolescente , Adulto , Anemia Aplástica/etiologia , Anemia Aplástica/mortalidade , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
19.
Biol Blood Marrow Transplant ; 24(12): 2501-2508, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30041010

RESUMO

Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P = .03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P = .02; and HR, 4.2; 95% CI, 1.7 to 9.9; P = .001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P = .005, HR, 3.8; 95% CI, 1.5 to 9.7; P = .005; and 3.2; 95% CI, 1.3 to 7.9; P = .01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.


Assuntos
Ciclofosfamida/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/cirurgia , Imunossupressores/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Transplante Haploidêntico/métodos , Adulto , Comorbidade , Ciclofosfamida/farmacologia , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Imunossupressores/farmacologia , Masculino , Recidiva Local de Neoplasia
20.
J Clin Apher ; 33(4): 521-528, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29971847

RESUMO

A consistent and reproducible depletion technique is crucial for the successful transplantation of an ex vivo depleted graft. Our aim was to evaluate the efficacy of an ex vivo technique for depletion of αß+ T cells using a biotinylated anti-TCRαß monoclonal antibody, which was performed by one clinical nurse specialist. Between 2012 and 2017, 119 depletion procedures from 216 apheresis using the anti-TCRαß monoclonal antibody were performed on 105 pediatric patients. The median log depletion of αß+ T cells was 4.0 (range, 2.5-5.0). The median recovery rates of CD34+ , NK, and γδ+ T cells were 90.4%, 74.9%, and 75.9%, respectively. The efficacy of depletion of αß+ T cells significantly improved over time and the duration of the depletion procedure significantly decreased over time. Our study demonstrated that this procedure for depletion of αß+ T cells by skilled staff is highly effective at depleting target cells and obtaining CD34+ progenitor cells.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Procedimentos de Redução de Leucócitos/métodos , Receptores de Antígenos de Linfócitos T alfa-beta/isolamento & purificação , Linfócitos T/imunologia , Transplante Haploidêntico/métodos , Adolescente , Antígenos CD34/análise , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
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